ArticleProceedings of the National Academy of Sciences of the United States of America2018
Chromatin modifiers Mdm2 and RNF2 prevent RNA:DNA hybrids that impair DNA replication.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- The expanding MDM2 universe.Cell death and differentiation · 2026Article
- MDM2 binds and suppresses RNA polymerase III to restrain the innate immune response to cytosolic DNA.Cell death and differentiation · 2026Article
- Allosteric network of dynamic coupling within BAP1-UCH revealed by methyl NMR.Nature communications · 2026Article
- EnP1 exploits H2Aub-dependent epigenetic reprogramming to promote microsporidia proliferation in host cells.PLoS pathogens · 2026Article
- Characterization of BRCA1-Associated Protein-1 (BAP1) Aggregation Properties Induced by Cancer-Associated Mutations.Chembiochem : a European journal of chemical biology · 2025Article
- Endurance training increases a ubiquitylated form of histone H3 in the skeletal muscle, supporting Notch1 upregulation in an MDM2-dependent manner.The Journal of physiology · 2025Article
- Transcription-Replication Conflicts: Unlocking New Frontiers in Cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Analysis of p53-Independent Functions of the Mdm2-MdmX Complex Using Data-Independent Acquisition-Based Profiling.Proteomes · 2025Article
- Z-form DNA-RNA hybrid blocks DNA replication.Nucleic acids research · 2025Article
- Cellular stress and epigenetic regulation in adult stem cells.Life science alliance · 2024Review
- A metabolic crosstalk between liposarcoma and muscle sustains tumor growth.Nature communications · 2024Article
- Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer.Cancer discovery · 2024Article
- PPM1D activity promotes the replication stress caused by cyclin E1 overexpression.Molecular oncology · 2024Article
- R-Loops in Genome Instability and Cancer.Cancers · 2023Review
- BAP1 as a guardian of genome stability: implications in human cancer.Experimental & molecular medicine · 2023Review
- BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability.Cell death and differentiation · 2022Article
- Sources, resolution and physiological relevance of R-loops and RNA-DNA hybrids.Nature reviews. Molecular cell biology · 2022Review
- Walking a tightrope: The complex balancing act of R-loops in genome stability.Molecular cell · 2022Review
- Hinokiflavone Inhibits MDM2 Activity by Targeting the MDM2-MDMX RING Domain.Biomolecules · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53-Mdm2 system is key to tumor suppression. We have recently reported that p53 as well as Mdm2 are capable of supporting DNA replication fork progression. On the other hand, we found that Mdm2 is a modifier of chromatin, modulating polycomb repressor complex (PRC)-driven histone modifications. Here we show that, similar to Mdm2 knockdown, the depletion of PRC members impairs DNA synthesis, as determined in fiber assays. In particular, the ubiquitin ligase and PRC1 component RNF2/Ring1B is required to support DNA replication, similar to Mdm2. Moreover, the Ring finger domain of Mdm2 is not only essential for its ubiquitin ligase activity, but also for proper DNA replication. Strikingly, Mdm2 overexpression can rescue RNF2 depletion with regard to DNA replication fork progression, and vice versa, strongly suggesting that the two ubiquitin ligases perform overlapping functions in this context. H2A overexpression also rescues fork progression upon depletion of Mdm2 or RNF2, but only when the ubiquitination sites K118/K119 are present. Depleting the H2A deubiquitinating enzyme BAP1 reduces the fork rate, suggesting that both ubiquitination and deubiquitination of H2A are required to support fork progression. The depletion of Mdm2 elicits the accumulation of RNA/DNA hybrids, suggesting R-loop formation as a mechanism of impaired DNA replication. Accordingly, RNase H overexpression or the inhibition of the transcription elongation kinase CDK9 each rescues DNA replication upon depletion of Mdm2 or RNF2. Taken together, our results suggest that chromatin modification by Mdm2 and PRC1 ensures smooth DNA replication through the avoidance of R-loop formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.